An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis

Abstract

Hypoxia and hypoxia induced overexpression of vascular endothelial growth factor (VEGF) not only seriously affects the treatment effects of photodynamic therapy (PDT) but also promotes tumor metastasis. Herein, an alternating irradiation strategy (referred to as alternate use of low/high dose of light [ALHDL] irradiation)-driven combination therapy of PDT and RNA interference (RNAi) is developed to synergistically inhibit tumor growth and metastasis. A cationic amphipathic peptide (ALS) served as a carrier in the co-delivery system of photochlor (HPPH) and siVEGF (ALSH/siVEGF). At the beginning of ALHDL-driven ALSH/siVEGF treatment, short-term LDL irradiation can facilitate the tumor penetration, cellular uptake, and endosome escape of ALSH/siVEGF. Moreover, accompanied by HDL-mediated rapid cell apoptosis and LDL-mediated efficient VEGF silencing, the joint use of PDT and RNAi achieved remarkable antitumor effects both in vitro and in vivo. Importantly, benefited from the excellent performance of ALHDL in slowing the rapid deterioration of the anoxic environment of tumors, and ALSH/siVEGF treatment-mediated highly improved VEGF silencing efficacy and inhibitory effect on angiogenesis, the liver and lung metastases of HeLa cells have been successfully suppressed. Together, this study clearly indicates that ALHDL-driven combination therapy of PDT and RNAi is a highly effective modality for inhibition of tumor growth and metastasis.

L‐Arg‐Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing

“…NH 2 ‐Lys(G 4 )‐OMe was synthesized as reported previously. [ 67 ] Stearic acid, N ‐Boc‐ethylenediamine hydrochloride, and anhydrous dimethyl sulfoxide (DMSO) were purchased from J&K Chemical Reagent Co., Ltd. (Beijing, China). Chlorine E6 was acquired from Frontier Scientific, Inc. N , N ‐diisopropylethylamine (DIPEA) and trifluoroacetic acid (TFA) were from Aladdin Reagents Company (Shanghai, China).…”

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

“…The upregulation of vascular endothelial growth factor (VEGF) and heat shock protein 70 (HSP-70) are the main causes of PDT tolerance. To obtain a more ideal PDT treatment effect, PS can be delivered together with gene therapy drugs or small molecule inhibitors targeting VEGF or HSP-70 [58]. In addition, NO produced by photostressed tumor cells can induce anti-PDT effect and enhance tumor aggressiveness.…”

Progress of Photodynamic and RNAi Combination Therapy in Cancer Treatment

“…Yue et al developed an alternate irradiation strategy for synergistic tumor treatment and metastasis inhibition, i.e. alternating low/high dose of light irradiation to achieve photodynamic and RNAi combined therapy . Therefore, PDT combined with RNAi to inhibit related targets has become a research hotspot in cancer treatment field.…”

“…alternating low/ high dose of light irradiation to achieve photodynamic and RNAi combined therapy. 43 Therefore, PDT combined with RNAi to inhibit related targets has become a research hotspot in cancer treatment field.…”